1. Field of the Invention
The present invention concerns combinations of zinc compounds furnishing zinc ions and one or more enzymes which may be a protease, a carbohydrase, or a lipase, or mixtures thereof.
Dental plaque forms as a deposit on and around teeth. It is a product of microbial growth, a dense microbial layer consisting of a mass of microorganisms embedded in a matrix, which accumulates on the tooth and adjacent surfaces. It has been reported that the microorganisms immediately after dental prophylaxis are mainly coccoidal organisms, which, in the mouths of some persons at least, change to filamentous organisms after a few days.
A wide variety of microorganisms are found in the oral cavity, some of which can produce acids or toxic materials. In addition to these microorganisms, dental plaque is composed of many other substances, such as mucoproteins and minerals derived from saliva, dead cells, and food residues which are dissolved, or present in particulate form. A major binding force holding plaque together is a matrix formed of the aforementioned mucoprotein or sticky polysaccharide substances secreted by some types of microorganisms.
Plaque deposition varies in extent throughout the oral cavity. Larger amounts tend to accumulate on those less accessible and more sheltered areas of teeth which cannot readily be reached with a toothbrush; rinsing with water alone usually will not dislodge such plaque. Plaque may also develop in pits and fissures of the teeth. It is extremely difficult to remove such plaque by mechanical means. With growth and multiplication of the bacteria, the plaque increases in size and becomes more viscous and thicker. The situation is exacerbated by the production by some microorganisms of a polysaccharide slime.
Recent dental research points to the fact that the major potential for harm by plaque resides in the bacterial component thereof. Bacterial metabolism can result in the production of acids, toxins and enzymes which are deleterious to the neighboring oral tissues. These materials can be retained in the mucoprotein matrix of the plaque and thus exert a direct influence on the adjacent tooth structures and gingivae. There is evidence pointing to plaque as being a direct cause of caries due to the generation of acids within its structure. Also, a direct correlation has been observed between the presence of dental plaque and the occurrence of gingivitis.
Dental calculus is a calcified or calcifying mass which is generated from dental plaque. In its more advanced state, it consists of an organic matrix, representing about 20% of the deposit and containing carbohydrates, proteins, bacteria, cellular debris, and other organic materials. The major portion of calculus is inorganic. This portion contains calcium, phosphorus, magnesium and lesser amounts of other mineral elements. The calcium and phosphorus are present primarily in the form of various calcium phosphate species, the most common of which is hydroxyapatite.
There are at least two well-recognized stages in calculus formation. First, the organic matrix or mucilaginous plaque (individually or simultaneously) deposits upon the tooth enamel or cementum, and may spread to adjacent areas in the oral cavity. At this stage, vigorous oral hygiene, especially tooth brushing, can remove much of the deposit and effectively reduce the amount of calculus subsequently found. In the second stage, alterations occur within the plaque which initiate mineralization. The exact mechanism whereby mineralization occurs has not yet been determined. Plaque tends to accumulate, selectively, calcium and phosphate. In one theory, it has been suggested that it is the activity of the microorganisms within the plaque which leads directly to the formation of dental calculus. Of the various types of bacteria present, the Leptothrix and Actinomyces appear to have been implicated most directly as being involved in both intercellular and extracellular mineralization. In another theory, it has been proposed that under appropriate conditions the mucilaginous matrix of the dental plaque is so altered as to promote mineralization. Here, too, the role of bacteria appears to be important; it has been observed that mineralization can start near the bacteria and that the bacteria are able to manufacture materials which are able to initiate the formation of insoluble calcium salts.
The clinical importance of plaque and calculus has been demonstrated many times over and an association between calculus and the occurrence of periodontal disease has long been observed. Removal of calculus is one of the most commonly practiced preventive measures against periodontal disease. As mentioned above, recent findings point toward plaque being involved in both carious lesion formation and in the initiation of peridontal disease even in the absence of calculus development. Thus, a direct correlation has been made between the appearance of plaque and gingivitis even in the absence of calculus.
2. The Prior Art
Prior to the instant invention, attempts have been made by others to retard the accumulation of dental calculus by means of zinc salts. M. T. Hanke in the Journal of the American Dental Association, Volume 27, September, 1940, page 1388, describes experiments to combat plaque with mouthwashes containing a variety of metallic salts, including zinc salts, having antifungal properties. The work of Hanke leads to the conclusion that the use of a zinc salt such as Hanke employed as the sole therapeutic agent has serious drawbacks, and that such zinc salts alone generally are not effective.
Also known is the use of soluble zinc salts as germicidal and deodorizing compounds, as set forth in U.S. Pat. No. 1,593,485 to Crosnier. This patent discloses that mixtures of zinc sulfophenate (i.e., phenolsulfonate) and zinc sulfate, chloride, or acetate are useful as bactericides and deodorants, the latter property being of value in slaughter-houses and the like where hydrogen sulfide is generated. However, there is no suggestion in this patent, nor in any other art known to the inventor, that a combination of zinc ions and an enzyme has unusually effective antiplaque and/or anticalculus properties.
The enzyme preparations tested in the past as plaque/calculus inhibitors have been of microbial, animal or vegetable origin. Crude mixtures of enzymes from various origins have also been used. Such mixtures have contained proteolytic, amylolytic and lipolytic activities. In some instances, the enzyme preparations tested have been relatively pure. The rationale for their use has been the hope that they could disrupt the plaque matrix or other structural component of plaque.
Enzyme preparations have found practical application in one instance, namely, the incorporation of such a material in a chewing gum vehicle, as disclosed in U.S. Pat. No. 3,235,460 to Ennever, wherein the use of pancreatin is discussed. The normal use of the chewing gum vehicle insures prolonged contact of the enzyme with the substrates it is intended to attack. Prolonged contact is required to obtain the proteolytic action of the product of Ennever's invention, which provides only 30% reduction in calculus after 8 weeks during which there was 25 minutes' contact per day.
The major difficulty in the practical use of enzymes as plaque and calculus inhibitors in other dental preparations is the need to realize rapid action at relatively low enzyme concentration, since dental preparations such as mouthwashes, toothpastes, tooth powders, etc. do not in their normal use involve the prolonged contact inherent in the use of enzymes contained in a chewing gum vehicle.
U.S. Pat. No. 3,194,738 to Harrisson and Packman discloses the use of enzymes in such vehicles as chewing gums, toothpastes, tablets, and mouthwashes, for retarding calculus formation.
U.S. Pat. No. 2,527,686 discloses a mouthwash containg about 0.16% zinc chloride, and about 16% total of a mixture of Papain and Malt.